Introduction/Background Vulvar cancer responds poorly to systemic treatment and in contrast to other gynecological cancers, targeted therapies remain at an early stage. Interactions of clinical, immune, and molecular biomarkers remain poorly understood for this rare cancer type. Here, we characterized the proteogenome of vulvar squamous cell carcinoma (vSCC) and provide a computational workflow to integrate publicly available data to study this rare and aggressive cancer type.
Methodology Whole exome sequencing, bulk RNA-sequencing, clinicopathological, and proteomics data from 23 patients with vSCC were analyzed. In addition, a total of 5543 women-derived TCGA genomic and transcriptomics sequencing data were obtained for this analysis.
Results Our cohort consisted of 34.8% human papillomavirus (HPV)+ and 65.2% HPV- vSCC patients. Early FIGO stage was significantly associated with HPV- status (12% (1/8) vs. 86% (12/15), p<0.001). TP53 and CDKN2 were mutually exclusive to HPV+. Patients being HPV+ revealed a higher frequency in PIK3CA alterations with 37.5% vs. 6.7% in HPV-. TYMS which is considered the primary site of action for 5-fluorouracil was significantly higher expressed in HPV+ patients (log2FC=1.7497, p<0.001). We identified unique single and doublet base substitution signatures in vSCC indicating defective DNA mismatch-repair and correlation with age. Tongue SCC (tSCC) was identified as a comparison cohort supported by different clustering methods of conjoint RNA-seq and clinicopathological data, derived from TCGA. vSCC was associated with elevated activated mast cells (p=0.0031), monocytes (p=0.0027), and M2 macrophages (p<0.001) compared to tSCC, independent of the HPV status.
Conclusion vSCC can be further distinguished by HPV status, somatic gene alterations and tumour microenvironment, while a similar cancer tissue has been identified with tSCC. Further analysis is targeted at identifying molecular signatures serving as biomarkers in vSCC and to suggest alternative treatment options of drugs already in use in tSCC or other cancer types.
Disclosures All authors declare that they have no conflicts of interest.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.